HPV-18-Immortalised Cells Require the Downregulation of the SncmtRNA-2/Hsa-miR-620 Axis During Cell Transformation

<i>Background and Objectives</i>: Non-coding RNAs (ncRNAs) are genetic transcripts that do not produce proteins but are increasingly recognised for their roles in cellular processes and disease. Specifically, ncRNAs are implicated in the landscape activation of molecular triggers for different diseases, including cancer and viral infections. The function of Sense non-coding mitochondrial RNA-2 (SncmtRNA-2) is currently unknown. This study aims to investigate the roles of SncmtRNA-2 and hsa-miR-620 in Ras-induced cellular transformation. <i>Materials and Methods</i>: The study utilized isoforms V, K, and H of the Ras oncogene and analysed the expression of SncmtRNA-2 and hsa-miR-620 in response to Ras activity. Additionally, both in silico and in vitro analyses were performed to assess whether PML mRNA is a putative target of hsa-miR-620 although direct binding to the PML 3'UTR was not experimentally tested. <i>Results</i>: The research demonstrated that transformation induced by Ras isoforms V, K, and H resulted in decreased expression of both SncmtRNA-2 and hsa-miR-620. Further investigation revealed that hsa-miR-620 is produced by the processing of SncmtRNA-2. It was also shown that Ras increases the expression of Promyelocytic Leukemia Protein (PML). In silico prediction combined with miR-620 gain and loss of function experiments supports PML as a putative hsa-miR-620 target. <i>Conclusions</i>: Ras promotes cellular transformation by decreasing the expression of SncmtRNA-2 and hsa-miR-620, which may contribute to increased PML expression, suggesting but not demonstrating a possible regulatory relationship among these molecules in HPV-immortalised cells. These results highlight a potential SncmtRNA-2/miR-620/PML axis that requires further validation through direct interaction assays and functional necessity/sufficiency experiments.